Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to investigate how a somatostatin analog (201-995 Sandoz), which is now commonly used for treatment of patients with gut hormone-producing tumors, affects water and ion absorption and transit time in the normal jejunum. Six healthy volunteers were given somatostatin analog intravenously at a dose of 1 microgram/kg/hr. At the same time, jejunal water and ion movement and transit time were measured using the triple-lumen tube technique [perfusion of a plasma-like electrolyte solution with PEG as a nonabsorbable marker at a rate of 15 ml/min; dye dilution curves ([3H]mannitol, [14C]PEG, BSP) for determination of jejunal transit time]. During somatostatin analog administration, transit time through a 30-cm segment of perfused jejunum increased from 4.0 min to 17.0 min. While the somatostatin analog increased jejunal transit time, it had no effect on net water and electrolyte absorption under steady-state conditions. The effect of somatostatin analog on the proximal small bowel is similar to the action of an eight-times higher dose of intravenous native somatostatin previously studied. The effect of the analog on transit time suggests a potentially beneficial effect in patients with large-volume diarrhea in which no tumor or circulating secretagogue can be identified, such as in pseudopancreatic cholera syndrome.
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PMID:Effect of somatostatin analog on water and electrolyte transport and transit time in human small bowel. 288 8

The cyclic analogue of somatostatin (SRIF), D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-NH2 (CTC), exhibits good affinity for both opioid and SRIF receptor systems. Its conformational properties were examined in water by high-field proton n.m.r. spectroscopy and compared with results previously obtained with structurally related analogues SMS 201-995 and Sandoz 204-090 in the same solvent. The assignments were made using 2 D-n.m.r. methods, especially long-range connectivities between neighbouring alpha protons, and between beta and aromatic protons. The 3JNH-C alpha H and delta delta/delta T values are compatible with an equilibrium between two gamma turns involving residues 2, 3 and 4 and residues 3, 4, and 5, respectively.
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PMID:Conformational study of a somatostatin analogue by high-field n.m.r. spectroscopy, in aqueous solution. 289 8

Somatostatin, a peptide hormone with a wide range of actions, was first described in 1973. It is found in neurons of the central and peripheral nervous systems and D cells of the gut and pancreas. Somatostatin acts as a neurotransmitter, a local tissue factor, and a hormone. The intrinsic metabolic effects of somatostatin have been well investigated during the past 10 years. It inhibits the release of gastrointestinal secretions and delays the absorption of glucose and amino acids. Somatostatin inhibits the effects of the release of several of the hormones involved in water-electrolyte homeostasis. It exerts an influence on the regulation of several endocrine and exocrine functions, acting as a "shock absorber". In the nervous system somatostatin functions as a neurotransmitter; intrathecal application causes characteristic changes in the motor system and behavioral aberrations. Furthermore, it has been suggested that it may be a potent analgesic. Side-effects seen during animal experiments are many: marked increases in blood glucose, various behavioral changes, respiratory failure, and death. This article compares the effects and potential side-effects of somatostatin with particular regard to the recent observation that this substance may be a potent analgesic.
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PMID:[Effects and side effects of somatostatin]. 289 83

We have measured the effects of intravenous infusion of calcitonin gene-related peptide at doses of 2.5, 10, and 50 pmol/kg.min on net jejunal water and solute fluxes and on plasma somatostatin concentrations in dogs. The hemodynamic effects and the pharmacokinetics of the peptide were also assessed. Using the triple-lumen perfusion technique in unsedated restrained animals it was shown that the highest dose of the peptide stimulated a transient net jejunal water and electrolyte secretion, and induced diarrhea in 4 of 6 animals receiving it. The peptide also induced dose-dependent tachycardia, hypotension, and increases in plasma immunoreactive somatostatin. All three doses of calcitonin gene-related peptide produced plasma immunoreactive peptide levels within the elevated range previously measured in human patients with medullary thyroid carcinoma. Calcitonin gene-related peptide may have a major role in the pathogenesis of secretory diarrhea in medullary thyroid carcinoma.
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PMID:Calcitonin gene-related peptide: enteric and cardiovascular effects in the dog. 290 Jul 92

Acidification of the gastric cardia has been shown to increase lower esophageal sphincter pressure (LESP). The mechanism by which this phenomenon occurs remains unknown. This study was undertaken to examine the effect and mechanism of action of proximal gastric acidification on LESP in the dog model. In long-term studies, acidification resulted in a significant increase in mean LESP (23.2 cm H2O). Pretreatment with either topical lidocaine or subcutaneous atropine blocked the sphincteric response to acidification. Neither truncal vagotomy and pyloroplasty, proximal gastric vagotomy, antral vagotomy and pyloroplasty, nor circumferential gastric myotomy significantly altered the sphincteric response to acid. Pretreatment with 6-hydroxydopamine or somatostatin also failed to alter the increase in LESP in response to acid. In short-term studies, after gastric transection 5 cm distal to the gastroesophageal junction, acidification of a vagally innervated distal gastric pouch produced a slight decrease in LESP, whereas acidification of the proximal (orad) section of gastric mucosa still resulted in a significant increase in LESP. These studies suggest that the increase in LESP observed with acidification of the gastric cardia is a local mechanism mediated by an intrinsic neural pathway dependent on cholinergic neurotransmission. This phenomenon of local reflex excitation may be another contributing mechanism to the barrier against gastroesophageal reflux.
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PMID:The mechanism of acid-induced increases in canine lower esophageal sphincter pressure. 292 55

Neither submucous ganglia, nor intestinal secretomotor reflexes are mentioned in the majority of the textbooks of physiology; because it has been realized only very recently that the submucous neurons may have important influences on whole body water and electrolyte balance. In the present review, we trace the rapid progress that has been made in determining the physiological properties of submucous neurons with known chemistry and projections in the guinea-pig small intestine, and we analyze how the work relates to studies in vivo of the neuronal control of intestinal trans-epithelial fluid transport. Four types of submucous neurons, which appear to be the full complement in the guinea-pig small intestine, have been identified through electrophysiological and histochemical analysis. (1) Cholinergic secretomotor neurons contain immunoreactivity for choline-acetyltransferase (ChAT), calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neuropeptide Y (NPY), somatostatin (SOM), and in the majority of cases galanin (GAL); these neurons project to the mucosal epithelium. (2) Non-cholinergic secretomotor neurons contain dynorphin (DYN), GAL and vasoactive intestinal peptide (VIP); these neurons project to the mucosa and provide collaterals to submucous arterioles. (3) Cholinergic interneurons contain ChAT alone; these neurons connect with the secretomotor neurons. (4) Presumed sensory neurons contain ChAT and substance P (SP) and have nerve endings in the mucosa. The two groups of secretomotor neurons receive cholinergic synaptic inputs from both myenteric and submucous ganglia. In addition, the DYN/GAL/VIP neurons receive sympathetic inhibitory inputs as well as inhibitory and non-cholinergic excitatory inputs from myenteric ganglia. The ChAT/SP nerve cells in submucous ganglia receive no or very ineffective inputs. From these data, from experiments on transmission from the neurons to the intestinal epithelium, and from studies of secretomotor reflexes in vivo, a correlated functional and structural circuitry of the submucous ganglia and their connections has been deduced. It is concluded that secretomotor reflexes are stimulated by the contents of the lumen during the digestion and absorption of food and that these reflexes cause a proportion of water and electrolytes that are absorbed with nutrients such as glucose to be returned to the lumen. The balance of absorption and secretion of water and electrolytes is controlled by sympathetic inhibitory inputs to secretomotor neurons, the activity in sympathetic pathways being varied to contribute to whole body water and electrolyte balance.
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PMID:Correlated electrophysiological and histochemical studies of submucous neurons and their contribution to understanding enteric neural circuits. 306 10

The effect of long-term administration of an antacid preparation on the gastric mucosa was investigated in rats, special attention was directed towards hypergastrinaemia and density of argyrophil cells. One ml of an Al (OH)3- and Mg (OH)2-containing antacid (in vitro neutralization capacity 28 mmol/die) or water was administered intragastrically 4 times daily. An additional group of rats remained untreated. Twelve hours after the final dose serum gastrin levels were significantly (p less than 0.001) elevated (113 +/- 28 pg/ml) compared to the control groups (33 +/- 1 and 22 +/- 2 pg/ml). Antral gastrin (G)-cell density was also increased after antacids by 58% whereas the somatostatin (D)-cell density and the somatostatin concentration in antral tissues were decreased. The number of fundic D- and argyrophil cells were not altered by antacid treatment. The number of parietal cell declined significantly in response to antacids. The foveolar gland region was almost doubled after antacids. It is concluded that in the rat 1. despite persistent hypergastrinaemia due to chronic antacid administration increases in argyrophil cell densities are not to be found; 2. long-term administration of antacids exert a trophic effect on the corpus mucosa predominantly by an increase of mucus neck cells.
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PMID:Influence of prolonged antacid administration on rat gastric mucosa. 314 98

The effect of the long-acting somatostatin analogue SMS 201-995 on renal function was investigated in nine cirrhotic patients with ascites, low urine output, low serum sodium, and normal serum creatinine. SMS 201-995, infused at 40 micrograms/h for 2 h, produced a significant increase in urine volume, a significant decrease in urine osmolality, and a significant increase in creatinine clearance. These changes, although less pronounced, persisted 24 h after the infusion of the analogue. No significant changes in free water clearance, urinary sodium excretion or serum sodium were noted. The effects of SMS 201-995 might be attributed to an improvement of renal haemodynamics through inhibition of vasoconstrictor systems acting in cirrhosis. It is concluded that SMS 201-995 may have a role in the treatment of the renal abnormalities complicating liver disease.
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PMID:Enhancement of renal function by a long-acting somatostatin analogue in patients with decompensated cirrhosis. 314 15

Central and lateral hypothalamic concentrations of 10 regulatory peptides were measured by radioimmunoassay in streptozocin-induced diabetic (STZ-D) and matched control rats between 1 day and 14 wk after diabetes induction. After 2 wk, both central and lateral hypothalamic neuropeptide Y (NPY) concentrations in STZ-D rats were consistently higher than those found in control rats, with significant 30-50% increases at 4 wk in the central hypothalamus, and at 6 and 14 wk in both central and lateral hypothalamus. Immunocytochemical studies in 4- and 6-wk STZ-D animals showed the appearance of intensely NPY-positive swollen cell bodies in the supraoptic nucleus and a subjective increase in NPY staining of medial hypothalamic nerve fibers. Central hypothalamic concentrations of three other peptides were significantly greater in STZ-D animals than those in control animals at single points (neurotensin, 1 day; calcitonin gene-related peptide, 2 wk; neurokinin, 4 wk). Hypothalamic concentrations of the other six peptides examined (bombesin, galanin, neuromedin B, substance P, somatostatin, and vasoactive intestinal peptide) did not differ significantly between STZ-D and control groups at any time. However, galanin immunostaining in the supraoptic and magnocellular paraventricular nuclei was strikingly concentrated in a reduced number of distended cell bodies. Hypothalamic peptide changes in STZ-D could be related to metabolic disturbance, changes in energy and water balance, altered pituitary function, or other factors. Persistently elevated concentrations of NPY, a very potent central stimulant of eating and drinking, may mediate the hyperphagia and polydipsia characteristic of STZ-D.
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PMID:Increased hypothalamic neuropeptide Y concentrations in diabetic rat. 328 97

The susceptibility of fetal endocrine pancreas to the diabetogenic action of cyproheptadine was investigated. Cyproheptadine (5 or 11 mg/kg) or water (control) was given orally once daily to pregnant rats on Days 13.5-20.5 or on Days 19.5-20.5 of gestation. Fetuses were obtained by cesarean section 24 hr after the last dose. Serum and pancreatic immunoreactive insulin and serum glucose from maternal and fetal animals were measured. Differences in maternal pancreatic insulin, serum insulin, and glucose between control and treated groups were not detected. In contrast, fetal pancreatic and serum insulin concentrations in animals exposed to 2 or 8 doses of cyproheptadine were less than 50% those of control. Drug treatment did not alter fetal pancreatic glucagon, pancreatic somatostatin, serum glucose, pancreas weight, or body weight. The drug-related depletion of fetal pancreatic insulin was reversible; the level returned to normal 3 days after cessation of the drug treatment. A similar depletion of fetal insulin was observed after 8 oral doses (11 mg/kg) of desmethylcyproheptadine, a metabolite which lacks the antiserotonin-antihistaminic properties of the parent compound. In vitro experiments showed that cyproheptadine inhibited the biosynthesis and release of insulin in fetal rat pancreas. These results indicate that cyproheptadine, when given to pregnant rats using a dose which produces no apparent effects in the maternal endocrine pancreas, causes abnormalities in the function of the insulin-secreting B cells in the fetal endocrine pancreas.
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PMID:Susceptibility of fetal rat endocrine pancreas to the diabetogenic action of cyproheptadine. 352 Sep 54


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